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Randomized Controlled Trial
. 2010 Sep 30;363(14):1324-34.
doi: 10.1056/NEJMoa0911123.

Anti-GD2 Antibody With GM-CSF, interleukin-2, and Isotretinoin for Neuroblastoma

Free PMC article
Randomized Controlled Trial

Anti-GD2 Antibody With GM-CSF, interleukin-2, and Isotretinoin for Neuroblastoma

Alice L Yu et al. N Engl J Med. .
Free PMC article


Background: Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma.

Methods: Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis.

Results: A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66±5% vs. 46±5% at 2 years, P=0.01) and overall survival (86±4% vs. 75±5% at 2 years, P=0.02 without adjustment for interim analyses).

Conclusions: Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma. (Funded by the National Institutes of Health and the Food and Drug Administration; number, NCT00026312.)


Figure 1
Figure 1. Enrollment, Randomization, and Follow-up of the Study Patients
Patients receiving protocol therapy were still being treated with isotretinoin, with or without immunotherapy, at the time the data were analyzed.
Figure 2
Figure 2. Kaplan–Meier Estimates of Survival among the 226 Study Patients Who Had Been Randomly Assigned, According to Treatment Group
Data are shown for event-free survival (Panel A) and overall survival (Panel B) for all 226 patients and for event-free survival (Panel C) and overall survival (Panel D) for the 179 patients 1 year of age or older at enrollment. The estimated survival (±SE) at 2 years is indicated in each plot.

Comment in

  • Antibody therapy and neuroblastoma.
    Tao X. Tao X. N Engl J Med. 2011 Jan 20;364(3):289; author reply 289-90. doi: 10.1056/NEJMc1012160. N Engl J Med. 2011. PMID: 21247330 No abstract available.

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